A healthy vaginal flora is characterized by an acidic environment inhabited predominantly by lactic acid bacteria, primarily species of Lactobacillus. The species distribution differs between women of different geographical background, race, age, life style and so on. The vaginal Lactobacilli are believed to have a protective effect against vaginal colonisation by pathogenic microorganisms. The exact mechanism is not known, but the maintenance of a pH of approximately 4, in which few other microorganisms can survive, seems to play an important role.
However, several factors may contribute to the disturbance of the vaginal flora. A well-known factor is antibiotic therapy, which aims to kill pathogenic bacteria, but which is known to significantly reduce the amount of Lactobacilli in the vagina. Another important factor are hormonal changes, in particular changes in estrogen levels, which are observed in several phases of a woman's life, for example in the peri-menopausal period. Also pH increases, for example due to sexual intercourse, may disturb the vaginal flora, since other bacteria may start to flourish once the vaginal pH increases. Disturbance of the vaginal flora may lead to vaginal disorders, in particular to (vulvo)vaginal candidiasis and bacterial vaginosis, which are two common vaginal disorders which affect many women worldwide.
Vaginal candidiasis is a yeast infection of the vagina involving overgrowth of the yeast Candida albicans. It is frequently observed after antibiotic treatment, which reduces the population of Lactobacilli. Bacterial vaginosis is characterised by a depletion of vaginal Lactobacilli accompanied by an overgrowth of a mixed vaginal flora of other bacteria. It may increase a woman's susceptibility to other vaginal problems, infections, pre-term labour and HIV.
The vaginal flora can be restored by replenishing or supplementing the disturbed vaginal flora with acid producing bacteria from an external source. These compounds comprising beneficial live bacteria, in particular lactic acid producing bacteria, such as Lactobacilli, are the so-called probiotic compounds. For example, WO 03/080813 describes novel Lactobacillus strains which can be used in absorbent products or vaginal capsules to restore vaginal flora. WO 98/47374 describes Bacillus spores for vaginal application.
Alternatively, the vaginal flora may be restored by prebiotics, which are nutrients for the probiotics and which selectively promote the growth of probiotics, because these nutrients are not, or not readily, digested by other microorganisms. Oligosaccharides, in particular fructooligosaccharides, are well-known prebiotics. EP 0 591 443 describes a vaginal gel containing specific oligosaccharides for restoring the vaginal flora. The vaginal flora may also be restored by agents which improve the environmental conditions for probiotic growth or which inhibit the growth or adhesion to the host tissues of pathogens. EP 2 343 088 describes a vaginal suppository which contains an anti-mycotic to inhibit the growth of pathogenic fungi. US 2011/0098357 and EP 0 257 007 describe a vaginal suppository comprising lactic acid for restoring the vaginal pH and thus restoring the vaginal flora.
Prebiotic and probiotic therapy may be combined for a synergistic effect. WO 97/29762 describes synbiotic formulations for vaginal use, such as capsules, tablets and suppositories. WO 03/080813 describes synbiotic vaginal capsules. Using these synbiotics, probiotic colonisation should be achieved faster than when only prebiotics or probiotics are provided, because the probiotics provided do not have to compete for nutrients in the vagina.
Vaginal synbiotics in dry form have the disadvantage that they are dependent on the limited moisture in the vagina to dissolve and reach their full efficacy. On the other hand, it is not desirable to provide these synbiotics in liquid form, because probiotics are moisture-sensitive and moisture will limit the shelf life of the probiotic product.